| Автор | PINTO, LAWRENCE H. |
| Автор | VITATERNA, MARTHA H. |
| Автор | SHIMOMURA, KAZUHIRO |
| Автор | SIEPKA, SANDRA M. |
| Автор | BALANNIK, VICTORIA |
| Автор | MCDEARMON, ERIN L. |
| Автор | OMURA, CHIAKI |
| Автор | LUMAYAG, STEPHEN |
| Автор | INVERGO, BRANDON M. |
| Автор | GLAWE, BRETT |
| Автор | CANTRELL, DONALD R. |
| Автор | INAYAT, SAMSOON |
| Автор | OLVERA, MARISSA A. |
| Автор | VESSEY, KIRSTAN A. |
| Автор | McCALL, MAUREEN A. |
| Автор | MADDOX, DENNIS |
| Автор | MORGANS, CATHERINE W. |
| Автор | YOUNG, BRANDON |
| Автор | PLETCHER, MATHEW T. |
| Автор | MULLINS, ROBERT F. |
| Автор | TROY, JOHN B. |
| Автор | TAKAHASHI, JOSEPH S. |
| Дата выпуска | 2007 |
| dc.description | We performed genome-wide chemical mutagenesis of C57BL/6J mice using N-ethyl-N-nitrosourea (ENU). Electroretinographic screening of the third generation offspring revealed two G3 individuals from one G1 family with a normal a-wave but lacking the b-wave that we named nob4. The mutation was transmitted with a recessive mode of inheritance and mapped to chromosome 11 in a region containing the Grm6 gene, which encodes a metabotropic glutamate receptor protein, mGluR6. Sequencing confirmed a single nucleotide substitution from T to C in the Grm6 gene. The mutation is predicted to result in substitution of Pro for Ser at position 185 within the extracellular, ligand-binding domain and oocytes expressing the homologous mutation in mGluR6 did not display robust glutamate-induced currents. Retinal mRNA levels for Grm6 were not significantly reduced, but no immunoreactivity for mGluR6 protein was found. Histological and fundus evaluations of nob4 showed normal retinal morphology. In contrast, the mutation has severe consequences for visual function. In nob4 mice, fewer retinal ganglion cells (RGCs) responded to the onset (ON) of a bright full field stimulus. When ON responses could be evoked, their onset was significantly delayed. Visual acuity and contrast sensitivity, measured with optomotor responses, were reduced under both photopic and scotopic conditions. This mutant will be useful because its phenotype is similar to that of human patients with congenital stationary night blindness and will provide a tool for understanding retinal circuitry and the role of ganglion cell encoding of visual information. |
| Издатель | Cambridge University Press |
| Тема | Chemical mutagenesis |
| Тема | Forward genetics |
| Тема | Retina |
| Тема | Retinal ganglion cells |
| Тема | Depolarizing bipolar cells |
| Тема | Congenital stationary night blindness |
| Тема | ON pathway |
| Тема | Molecular cloning |
| Тема | Positional cloning |
| Тема | Gene discovery |
| Тема | Rod pathway |
| Тема | Visual acuity |
| Название | Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse |
| DOI | 10.1017/S0952523807070149 |
| Electronic ISSN | 1469-8714 |
| Print ISSN | 0952-5238 |
| Журнал | Visual Neuroscience |
| Том | 24 |
| Первая страница | 111 |
| Последняя страница | 123 |
| Аффилиация | PINTO LAWRENCE H.; Northwestern University; Northwestern University |
| Аффилиация | VITATERNA MARTHA H.; Northwestern University |
| Аффилиация | SHIMOMURA KAZUHIRO; Northwestern University |
| Аффилиация | SIEPKA SANDRA M.; Northwestern University |
| Аффилиация | BALANNIK VICTORIA; Northwestern University |
| Аффилиация | MCDEARMON ERIN L.; Northwestern University; Northwestern University |
| Аффилиация | OMURA CHIAKI; Northwestern University |
| Аффилиация | LUMAYAG STEPHEN; Northwestern University |
| Аффилиация | INVERGO BRANDON M.; Northwestern University |
| Аффилиация | GLAWE BRETT; Northwestern University |
| Аффилиация | CANTRELL DONALD R.; McCormick School of Engineering Northwestern University |
| Аффилиация | INAYAT SAMSOON; McCormick School of Engineering Northwestern University; University of Engineering and Technology |
| Аффилиация | OLVERA MARISSA A.; University of Iowa |
| Аффилиация | VESSEY KIRSTAN A.; University of Louisville |
| Аффилиация | McCALL MAUREEN A.; University of Louisville; University of Louisville |
| Аффилиация | MADDOX DENNIS; The Jackson Laboratory |
| Аффилиация | MORGANS CATHERINE W.; Oregon Health and Science University |
| Аффилиация | YOUNG BRANDON; The Scripps Research Institute |
| Аффилиация | PLETCHER MATHEW T.; The Scripps Research Institute |
| Аффилиация | MULLINS ROBERT F.; University of Iowa |
| Аффилиация | TROY JOHN B.; McCormick School of Engineering Northwestern University |
| Аффилиация | TAKAHASHI JOSEPH S.; Northwestern University; Northwestern University |
| Выпуск | 1 |
